Byssinosis is an occupational pulmonary disease associated with the inhalation of cotton and other textile dusts. In many healthy subjects never before exposed to cotton dust, the symptoms (e.g, tightness in chest and shortness of breath) and physiologic changes (e.g, changes in pulmonary function) of early byssinosis can be reproduced by the inhalation of an aerosol of water-soluble extract of cotton bract. The mechanism by which cotton bract extract (CBE) induces obstruction of the airways in healthy subjects is unclear. Recent evidence has suggested that a generalized inflammatory reaction may be responsible for acute and subacute byssinotic changes. If this is indeed the case, one might expect airway hyperresponsiveness to result from CBE exposure. Characterization of changes in human airway responsiveness is therefore an important link between our animal models and clinical manifestations in cotton textile workers. We propose to examine changes in airway hyperreactivity from baseline values at three time points following CBE exposure: 3 hours, 24 hours, and 1 week later. This will be achieved by measurement of response to methacholine inhalation at doses of 1, 10, 30, & 100 mg/ml, and in a second part of the study, measurement of response to 10, 30, 100, 300, 1000 and 3000 mcg of metaproterenol inhalation. The effect of normal saline aerosol (placebo) on the response to methacholine and metaproterenol dose-response will also be measured and evaluated in a random, cross-over design. Measurements of response to methacholine and metaproterenol will be evaluated in both reactors and non-reactors to CBE. This is important since changes in airway hyperreactivity have been shown to be present in the absence of lung function changes resulting from the provocative agent itself, e.g. ozone. Lung function assessment will be made with maximal and partial flow-volume curves. We will attempt to reduce airway hyperreactivity caused by CBE using pretreatment with the anti-inflammatory drugs indomethacin and prednisone. Characterizing airway reactivity following CBE inhalations is important since it may help explain sustained symptoms in workers and may also help characterize interactions between cotton dust and other irritants such as cigarette smoke. Finally, the data obtained may help explain how repeated acute responses may eventually lead to chronic disease in textile workers.